Decoding Dysfunction in Duchenne Muscular Dystrophy Cardiomyopathy
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See Article by Yamamoto et al
Duchenne muscular dystrophy (DMD) is an X-linked disorder diagnosed in childhood that is characterized by rapidly progressive and life-limiting loss of muscle function. The DMD gene is the largest known gene in humans, comprising 79 exons. Exonic out-of-frame mutations produce truncated or absent dystrophin protein. As a result, cardiac and skeletal myocytes lose their plasma membrane integrity and contractile ability, leading to muscle weakness. DMD affects ≈1 in every 5000 live male births, and these individuals usually die before reaching the third decade of life.1 With advances in pulmonary and neuromuscular care over the past few decades, DMD cardiomyopathy has emerged as a principal cause of morbidity and mortality in patients with this disease.2 DMD cardiomyopathy is characterized by left ventricular (LV) dysfunction, atrial and ventricular arrhythmias, and a higher mortality than other pediatric dilated cardiomyopathies. Early detection and management are associated with delayed progression of LV dysfunction and with lower mortality. However, overall, DMD cardiomyopathy remains under-recognized and undertreated.3–5 Genotype–phenotype correlations relating the genetic location of the dystrophin mutation to age of onset of dilated cardiomyopathy have been reported in other dystrophinopathies; however, the associations are less clear in DMD.6
In this issue of Circulation: Genomic and Precision Medicine, Yamamoto et al7 aim to elucidate relationships between deficiencies in 4 dystrophin tissue-specific isoforms and cardiac dysfunction based on 2-dimensional echocardiographic parameters. The 4 isoforms examined were Dp260, which is expressed in the retina; Dp140, which is expressed in …